Phospholipid-transporting ATPase IA

Details

Name
Phospholipid-transporting ATPase IA
Kind
protein
Synonyms
  • 7.6.2.1
  • ATPase class I type 8A member 1
  • ATPIA
  • Chromaffin granule ATPase II
  • P4-ATPase flippase complex alpha subunit ATP8A1
Gene Name
ATP8A1
UniProtKB Entry
Q9Y2Q0Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0001993|Phospholipid-transporting ATPase IA
MPTMRRTVSEIRSRAEGYEKTDDVSEKTSLADQEEVRTIFINQPQLTKFCNNHVSTAKYN
IITFLPRFLYSQFRRAANSFFLFIALLQQIPDVSPTGRYTTLVPLLFILAVAAIKEIIED
IKRHKADNAVNKKQTQVLRNGAWEIVHWEKVAVGEIVKVTNGEHLPADLISLSSSEPQAM
CYIETSNLDGETNLKIRQGLPATSDIKDVDSLMRISGRIECESPNRHLYDFVGNIRLDGH
GTVPLGADQILLRGAQLRNTQWVHGIVVYTGHDTKLMQNSTSPPLKLSNVERITNVQILI
LFCILIAMSLVCSVGSAIWNRRHSGKDWYLNLNYGGASNFGLNFLTFIILFNNLIPISLL
VTLEVVKFTQAYFINWDLDMHYEPTDTAAMARTSNLNEELGQVKYIFSDKTGTLTCNVMQ
FKKCTIAGVAYGHVPEPEDYGCSPDEWQNSQFGDEKTFSDSSLLENLQNNHPTAPIICEF
LTMMAVCHTAVPEREGDKIIYQAASPDEGALVRAAKQLNFVFTGRTPDSVIIDSLGQEER
YELLNVLEFTSARKRMSVIVRTPSGKLRLYCKGADTVIYDRLAETSKYKEITLKHLEQFA
TEGLRTLCFAVAEISESDFQEWRAVYQRASTSVQNRLLKLEESYELIEKNLQLLGATAIE
DKLQDQVPETIETLMKADIKIWILTGDKQETAINIGHSCKLLKKNMGMIVINEGSLDGTR
ETLSRHCTTLGDALRKENDFALIIDGKTLKYALTFGVRQYFLDLALSCKAVICCRVSPLQ
KSEVVEMVKKQVKVVTLAIGDGANDVSMIQTAHVGVGISGNEGLQAANSSDYSIAQFKYL
KNLLMIHGAWNYNRVSKCILYCFYKNIVLYIIEIWFAFVNGFSGQILFERWCIGLYNVMF
TAMPPLTLGIFERSCRKENMLKYPELYKTSQNALDFNTKVFWVHCLNGLFHSVILFWFPL
KALQYGTAFGNGKTSDYLLLGNFVYTFVVITVCLKAGLETSYWTWFSHIAIWGSIALWVV
FFGIYSSLWPAIPMAPDMSGEAAMLFSSGVFWMGLLFIPVASLLLDVVYKVIKRTAFKTL
VDEVQELEAKSQDPGAVVLGKSLTERAQLLKNVFKKNHVNLYRSESLQQNLLHGYAFSQD
ENGIVSQSEVIRAYDTTKQRPDEW
Number of residues
1164
Molecular Weight
131368.215
Theoretical pI
6.83
GO Classification
Functions
ATP hydrolysis activity / ATPase-coupled intramembrane lipid transporter activity / ATPase-coupled monoatomic cation transmembrane transporter activity / phosphatidylserine flippase activity / phosphatidylserine floppase activity
Processes
aminophospholipid translocation / monoatomic ion transmembrane transport / transport across blood-brain barrier
Components
azurophil granule membrane / cytoplasmic vesicle / cytosol / organelle membrane / phospholipid-translocating ATPase complex / specific granule membrane / synaptic vesicle membrane / trans-Golgi network
General Function
Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (PubMed:31416931). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. In vitro, its ATPase activity is selectively and stereospecifically stimulated by phosphatidylserine (PS) (PubMed:31416931). The flippase complex ATP8A1:TMEM30A seems to play a role in regulation of cell migration probably involving flippase-mediated translocation of phosphatidylethanolamine (PE) at the cell membrane (By similarity). Acts as aminophospholipid translocase at the cell membrane in neuronal cells (By similarity)
Specific Function
ATP binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
66-86 93-115 298-319 345-366 858-878 891-910 941-962 977-999 1006-1026 1045-1070
Cellular Location
Cytoplasmic vesicle, secretory vesicle, chromaffin granule membrane
Gene sequence
>lcl|BSEQ0019050|Phospholipid-transporting ATPase IA (ATP8A1)
ATGCCCACCATGCGGAGGACCGTGTCGGAGATCCGCTCGCGCGCCGAAGGTTATGAGAAG
ACAGATGATGTTTCAGAGAAGACCTCACTGGCTGACCAGGAGGAAGTAAGGACTATTTTC
ATCAACCAGCCCCAGCTGACAAAATTCTGCAATAACCATGTCAGCACTGCAAAATACAAC
ATAATCACATTCCTTCCAAGATTTCTCTACTCTCAGTTCAGAAGAGCTGCTAATTCATTT
TTTCTCTTTATTGCACTGCTGCAGCAAATACCTGATGTGTCACCAACAGGTCGTTATACA
ACACTGGTTCCTCTCTTATTTATTTTAGCTGTGGCAGCTATCAAAGAGATAATAGAAGAT
ATTAAACGACATAAAGCTGATAATGCAGTGAACAAGAAACAAACGCAAGTTTTGAGAAAT
GGTGCTTGGGAAATTGTCCACTGGGAAAAGGTAAATGTTGGAGATATAGTTATAATAAAA
GGCAAAGAGTATATACCTGCTGACACTGTACTTCTCTCATCAAGTGAGCCCCAAGCCATG
TGCTACATTGAAACATCCAACTTAGATGGTGAAACAAACTTGAAAATTAGACAGGGCTTA
CCAGCAACATCAGATATCAAAGACGTTGACAGTTTGATGAGGATTTCTGGCAGAATTGAG
TGTGAAAGTCCAAACAGACATCTCTACGATTTTGTTGGAAACATAAGGCTTGATGGACAT
GGCACCGTTCCACTGGGAGCAGATCAGATTCTTCTTCGAGGAGCTCAGTTGAGAAATACA
CAGTGGGTTCATGGAATAGTTGTCTACACTGGACATGACACCAAGCTGATGCAGAATTCA
ACAAGTCCACCACTTAAGCTCTCAAATGTGGAACGGATTACAAATGTACAAATTTTGATT
TTATTTTGTATCTTAATTGCCATGTCTCTTGTCTGTTCTGTGGGCTCAGCCATTTGGAAT
CGAAGGCATTCTGGAAAAGACTGGTATCTCAATCTAAACTATGGTGGCGCTAGTAATTTT
GGACTGAATTTCTTGACCTTCATCATCCTTTTCAACAATCTCATTCCTATCAGCTTATTG
GTTACATTAGAAGTTGTGAAATTTACCCAGGCATACTTCATAAATTGGGATCTTGACATG
CACTATGAACCCACAGACACTGCTGCTATGGCTCGAACATCTAATCTGAATGAGGAACTT
GGCCAGGTTAAATACATATTTTCTGACAAAACTGGTACTCTGACATGCAATGTAATGCAG
TTTAAGAAGTGCACCATAGCGGGAGTTGCTTATGGGCAGAACTCACAGTTTGGAGATGAA
AAAACATTTAGTGATTCATCATTGCTGGAAAATCTCCAAAATAATCATCCAACTGCACCT
ATAATATGTGAATTTCTTACAATGATGGCAGTCTGTCACACAGCAGTGCCAGAGCGAGAA
GGTGACAAGATTATTTATCAAGCAGCATCTCCAGATGAGGGAGCATTGGTCAGAGCAGCC
AAGCAATTGAATTTTGTTTTCACTGGAAGAACACCCGACTCGGTGATTATAGATTCACTG
GGGCAGGAAGAAAGATATGAATTGCTCAATGTCTTGGAGTTTACCAGTGCTAGGAAAAGA
ATGTCAGTGATTGTTCGCACTCCATCTGGAAAGTTACGACTCTACTGCAAAGGAGCTGAC
ACTGTAATTTATGATCGACTGGCAGAGACGTCAAAATACAAAGAAATTACCCTAAAACAT
TTAGAGCAGTTTGCTACAGAAGGGTTAAGAACTTTATGTTTTGCTGTGGCTGAGATTTCA
GAGAGCGACTTTCAGGAGTGGCGAGCAGTCTATCAGCGAGCATCTACATCTGTGCAGAAC
AGGCTACTCAAACTCGAAGAGAGTTATGAGTTGATTGAAAAGAATCTTCAGCTACTTGGA
GCAACAGCCATTGAGGATAAATTACAAGATCAAGTGCCTGAAACCATAGAAACGCTAATG
AAAGCAGACATCAAAATCTGGATCCTTACAGGGGACAAGCAAGAAACTGCCATTAACATC
GGACACTCCTGCAAACTGTTGAAGAAGAACATGGGAATGATTGTTATAAATGAAGGCTCT
CTTGATGGAACAAGGGAAACTCTCAGTCGTCACTGTACTACCCTTGGTGATGCTCTCCGG
AAAGAGAATGATTTTGCTCTTATAATTGATGGGAAAACCCTCAAATATGCCTTAACCTTT
GGAGTACGACAGTATTTCCTGGACTTAGCTTTGTCATGCAAAGCTGTCATTTGCTGTCGG
GTTTCTCCTCTTCAAAAATCTGAAGTTGTTGAGATGGTTAAGAAACAAGTCAAAGTCGTA
ACGCTTGCAATCGGTGATGGAGCAAATGATGTCAGCATGATACAGACAGCGCACGTTGGT
GTTGGTATCAGTGGCAATGAAGGCCTGCAGGCAGCTAATTCCTCTGACTACTCCATAGCT
CAGTTCAAATATTTGAAGAATTTACTGATGATTCATGGTGCCTGGAACTATAACAGAGTC
TCCAAGTGCATCTTATACTGCTTCTACAAGAATATAGTGCTCTATATTATCGAGATCTGG
TTTGCCTTTGTTAATGGCTTTTCTGGACAGATCCTCTTTGAAAGATGGTGTATAGGTCTC
TATAACGTGATGTTTACAGCAATGCCTCCTTTAACTCTTGGAATATTTGAGAGATCATGC
AGAAAAGAGAACATGTTGAAGTACCCTGAATTATACAAAACATCTCAGAATGCCCTGGAC
TTCAACACCAAGGTTTTCTGGGTTCATTGTTTAAATGGCCTCTTCCACTCAGTTATTCTG
TTTTGGTTTCCACTAAAAGCCCTTCAGTATGGTACTGCATTTGGAAATGGGAAAACCTCG
GATTATCTGCTACTGGGAAACTTTGTGTACACTTTTGTGGTGATAACTGTGTGTTTGAAA
GCTGGATTGGAGACATCATATTGGACATGGTTCAGCCACATAGCGATATGGGGGAGCATC
GCACTCTGGGTGGTGTTTTTTGGAATCTACTCATCTCTGTGGCCTGCCATTCCGATGGCC
CCTGATATGTCAGGAGAGGCAGCCATGTTGTTCAGTTCTGGAGTCTTTTGGATGGGCTTG
TTATTCATCCCTGTGGCATCTCTGCTCCTTGATGTGGTGTACAAGGTTATCAAGAGGACT
GCTTTTAAAACATTGGTCGATGAAGTTCAGGAGCTGGAGGCAAAATCTCAAGACCCAGGA
GCAGTTGTACTTGGAAAAAGCCTGACCGAGAGGGCGCAACTGCTCAAGAACGTCTTTAAG
AAGAACCACGTGAACTTGTACCGCTCTGAATCCTTGCAACAAAATCTGCTCCATGGGTAT
GCGTTCTCTCAAGATGAAAATGGAATCGTTTCACAGTCTGAAGTGATAAGAGCATATGAT
ACCACGAAACAGAGGCCCGACGAATGGTGA
Chromosome Location
4
Locus
4p13
External Identifiers
ResourceLink
UniProtKB IDQ9Y2Q0
UniProtKB Entry NameAT8A1_HUMAN
GenBank Protein ID4972583
GenBank Gene IDAF067820
GeneCard IDATP8A1
GenAtlas IDATP8A1
HGNC IDHGNC:13531
PDB ID(s)6K7G, 6K7H, 6K7I, 6K7J, 6K7K, 6K7L, 6K7M, 6K7N
KEGG IDhsa:10396
NCBI Gene ID10396
General References
  1. Mouro I, Halleck MS, Schlegel RA, Mattei MG, Williamson P, Zachowski A, Devaux P, Cartron JP, Colin Y: Cloning, expression, and chromosomal mapping of a human ATPase II gene, member of the third subfamily of P-type ATPases and orthologous to the presumed bovine and murine aminophospholipid translocase. Biochem Biophys Res Commun. 1999 Apr 13;257(2):333-9. [Article]
  2. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [Article]
  5. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  6. van der Velden LM, Wichers CG, van Breevoort AE, Coleman JA, Molday RS, Berger R, Klomp LW, van de Graaf SF: Heteromeric interactions required for abundance and subcellular localization of human CDC50 proteins and class 1 P4-ATPases. J Biol Chem. 2010 Dec 17;285(51):40088-96. doi: 10.1074/jbc.M110.139006. Epub 2010 Oct 14. [Article]
  7. Bryde S, Hennrich H, Verhulst PM, Devaux PF, Lenoir G, Holthuis JC: CDC50 proteins are critical components of the human class-1 P4-ATPase transport machinery. J Biol Chem. 2010 Dec 24;285(52):40562-72. doi: 10.1074/jbc.M110.139543. Epub 2010 Oct 20. [Article]
  8. Takatsu H, Baba K, Shima T, Umino H, Kato U, Umeda M, Nakayama K, Shin HW: ATP9B, a P4-ATPase (a putative aminophospholipid translocase), localizes to the trans-Golgi network in a CDC50 protein-independent manner. J Biol Chem. 2011 Nov 4;286(44):38159-67. doi: 10.1074/jbc.M111.281006. Epub 2011 Sep 13. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Phosphatidyl serineinvestigational, nutraceuticalunknowntargetDetails